ArticleCancer research2016
Melanoma Cells Block PEDF Production in Fibroblasts to Induce the Tumor-Promoting Phenotype of Cancer-Associated Fibroblasts.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Review
- Comparative omics reveals conserved extracellular matrix signatures during mammary tumor progression.Frontiers in oncology · 2026Article
- Association between cardiovascular disease and non-melanoma skin cancer: The mediation effect of obesity and inflammation.PloS one · 2026Article
- Melanoma-Keratinocyte Crosstalk Participates in Melanoma Progression with Mechanisms Partially Overlapping with Those of Cancer-Associated Fibroblasts.International journal of molecular sciences · 2025Article
- Diagnostic, Therapeutic and Prognostic Potential of Pigment Epithelium-Derived Factor in Cancer.International journal of molecular sciences · 2025Review
- Extracellular nicotinamide phosphoribosyltransferase visfatin activates JAK2-STAT3 pathway in cancer-associated fibroblasts to promote colorectal cancer metastasis.Genes & genomics · 2025Article
- The Various Roles of PEDF in Cancer.Cancers · 2024Review
- Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment.Cellular and molecular neurobiology · 2023Review
- Thyroid Cancer and Fibroblasts.Cancers · 2022Review
- PEDF is an antifibrosis factor that inhibits the activation of fibroblasts in a bleomycin-induced pulmonary fibrosis rat model.Respiratory research · 2022Article
- Influence of Tumor Microenvironment and Fibroblast Population Plasticity on Melanoma Growth, Therapy Resistance and Immunoescape.International journal of molecular sciences · 2021Review
- Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration.Frontiers in cellular neuroscience · 2021Article
- Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance.Frontiers in oncology · 2021Review
- Natural products and other inhibitors of FEuropean journal of medicinal chemistry · 2020Review
- Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance.Cells · 2020Review
- Identification of four hub genes as promising biomarkers to evaluate the prognosis of ovarian cancer in silico.Cancer cell international · 2020Article
- Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma.Journal of gastroenterology · 2019Article
- p53 mediates PEDF‑induced autophagy in human umbilical vein endothelial cells through sestrin2 signaling.Molecular medicine reports · 2019Article
- Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance.Journal of oncology · 2019Review
- Pigment Epithelium-Derived Factor (PEDF) as a Regulator of Wound Angiogenesis.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Loss of pigment epithelium-derived factor (PEDF, SERPINF1) in cancer cells is associated with poor prognosis and metastasis, but the contribution of stromal PEDF to cancer evolution is poorly understood. Therefore, we investigated the role of fibroblast-derived PEDF in melanoma progression. We demonstrate that normal dermal fibroblasts expressing high PEDF levels attenuated melanoma growth and angiogenesis in vivo, whereas PEDF-depleted fibroblasts exerted tumor-promoting effects. Accordingly, mice with global PEDF knockout were more susceptible to melanoma metastasis. We also demonstrate that normal fibroblasts in close contact with PEDF-null melanoma cells lost PEDF expression and tumor-suppressive properties. Further mechanistic investigations underlying the crosstalk between tumor and stromal cells revealed that melanoma cells produced PDGF-BB and TGFβ, which blocked PEDF production in fibroblasts. Notably, cancer-associated fibroblasts (CAF) isolated from patient-derived tumors expressed markedly low levels of PEDF. Treatment of patient CAF and TGFβ-treated normal fibroblasts with exogenous PEDF decreased the expression of CAF markers and restored PEDF expression. Finally, expression profiling of PEDF-depleted fibroblasts revealed induction of IL8, SERPINB2, hyaluronan synthase-2, and other genes associated with tumor promotion and metastasis. Collectively, our results demonstrate that PEDF maintains tumor-suppressive functions in fibroblasts to prevent CAF conversion and illustrate the mechanisms by which melanoma cells silence stromal PEDF to promote malignancy. Cancer Res; 76(8); 2265-76. ©2016 AACR.
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